Patellar Osteomyelitis in a 9-Year-Old Patient with Chronic Granulomatous Disease: A Case Report

Hematogenous osteomyelitis is commonly reported in long tubular bones in the pediatric population. Acute osteomyelitis involving the patella is extremely uncommon in children, and its diagnosis is frequently delayed due to its rarity and variable clinical manifestations. Chronic granulomatous disease (CGD) is a rare genetic immunodeficiency disorder characterized by severe recurrent bacterial and fungal infections. The most commonly affected sites of infection are the lungs, lymph nodes, skin, liver, and gastrointestinal tract. Acute hematogenous osteomyelitis of the patella associated with CGD has never been reported. Our report describes the first case of acute hematogenous patellar osteomyelitis in a pediatric patient with CGD. Her clinical manifestations were similar to other possible differentials such as septic arthritis; however, use of advanced imaging confirmed the diagnosis, and the patient was successfully managed surgically. Since hematogenous osteomyelitis in children is uncommon, a high index of suspicion and advanced imaging may help with its diagnosis, and in cases where antibiotic treatment proves to be insufficient, prompt surgical management is imperative.

Revealing Chronic Granulomatous Disease in a Patient With Williams-Beuren Syndrome Using Whole Exome Sequencing

Blended phenotypes exhibited by a patient may present a challenge to the establishment of diagnosis. In this study, we report a seven-year-old Murut girl with unusual features of Williams-Beuren syndrome (WBS), including recurrent infections and skin abscesses. Considering the possibility of a second genetic disorder, a mutation screening for genes associated with inborn errors of immunity (IEI) was conducted using whole exome sequencing (WES). Analysis of copy number variations (CNVs) from the exome data revealed a 1.53Mb heterozygous deletion on chromosome 7q11.23, corresponding to the known WBS. We also identified a biallelic loss of NCF1, which indicated autosomal recessive chronic granulomatous disease (CGD). Dihydrorhodamine (DHR) flow cytometric assay demonstrated abnormally low neutrophil oxidative burst activity. Coamplification of NCF1 and its pseudogenes identified a GT-deletion (ΔGT) at the start of exon 2 in NCF1 (NM_000265.7: c.75_76delGT: p.Tyr26Hisfs*26). Estimation of NCF1-to-NCF1 pseudogenes ratio using ΔGT and 20-bp gene scans affirmed nil copies of NCF1 in the patient. While the father had a normal ratio of 2:4, the mother had a ratio of 1:5, implicating the carrier of ΔGT-containing NCF1. Discovery of a 7q11.23 deletion involving one NCF1 allele and a ΔGT in the second NCF1 allele explained the coexistence of WBS and CGD in our patient. This study highlights the capability of WES to establish a molecular diagnosis for a case with blended phenotypes, enabling the provision of appropriate prophylactic treatment.